Interferon beta-1a is an interferon beta 1 agonist with the ability to up-regulate CD73, a molecule which yields anti-inflammatory adenosine, which enhances endothelial barrier function and leads to the prevention of vascular leakage, the predominant pathophysiological event in ARDS. Vascular leakage in ARDS allows plasma exudation into the alveolar space leading to potentially life-threatening hypoxaemia. Interferon beta-1a has the potential to reduce the impact of ARDS by reducing vascular leakage, but is not limited to this example.
As with all protein based pharmaceuticals, one major obstacle that must be overcome in the use of interferon beta (IFN-beta) as a therapeutic agent is the loss of pharmaceutical utility that can result from its instability in pharmaceutical formulations. Physical instabilities that threaten polypeptide activity and efficacy in pharmaceutical formulations include denaturation and formation of insoluble aggregates, while chemical instabilities include e.g. hydrolysis, oxidation and deamidation. Some of these changes are known to lead to the loss or reduction of the pharmaceutical bioactivity of the protein of interest. When small amounts of hormone peptides are administered, it is also crucial that the patient is guaranteed to receive the right dosing. Due to high lipophilic amino acid residue content in IFN-beta, it adheres to container surfaces and form aggregates, resulting in losses of active pharmaceutical ingredient.
Another requirement, especially for the drug products for use in the treatment of ARDS, is that the drug product has to be available in an emergency. Consequently, there is a need for stable lyophilised pharmaceutical formulations comprising IFN-beta 1a having long shelf life and preserving their pharmaceutical utility, and especially if freeze-dried, requiring careful control of dosing and in use stability during administration. These requirements are necessary for compounds administered intravenously, as the patient gets exposed to the drug instantly.